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Edition of 07 February 2020

International News

Survey on success factors of the Japanese and the United States Orphan Drug Programmes

According to a paper published in the American College of Clinical Pharmacology, the basic components of regulatory and supporting policies for orphan drug development appear similar between the United States and Japan, but the drugs designated as orphan drugs bare different between the 2 countries. The probabilities of development success, namely the marketing approval, in designated orphan drugs are also significantly different. The study analysed recent outcomes of development for orphan drugs designated from 1993 to 2017 in Japan, considering their development and approval status in the United States. Analysis showed that success for orphan drug development in Japan was apparently associated with prior approval status in the United States. Company size and orphan development experience were also positively associated with successful marketing approval. Similar designations and priority review systems for orphan drugs have been enacted within the two countries; however, economic incentives and regulatory conditions provided by the systems seem to be different between the two countries, which had probably lead to varied performance in orphan designation and approval.

China's new Drug Administration Law and its impact on medications for rare diseases

China’s new Drug Administration Law intended "to ensure drug safety, to protect the public's legitimate rights and interests and to protect and promote public health" has been announced. China’s new Drug Administration Law was amended in August 2019, and is a major piece of legislation governing drug administration in China. The new Drug Administration Law also states that the State will implement priority review and approval for drugs in short supply needed urgently clinically, such as for new drugs to prevent and treat serious infectious diseases, for drugs to treat rare diseases, and for paediatric drugs. It encourages the domestic manufacturing and provides a firm legal basis for medications. Ethics review, informed consent, clinical risks, and other aspects of "conducting clinical trials on drugs" are stipulated in the new China’s Drug Administration Law.

European News

2019 EJP RD Joint Transnational Call results are out

The results of the European Joint Programme Rare Disease (EJP RD) first joint transnational call, launched in December 2018, have been published. 217 eligible pre-proposals were submitted during the first step and were examined by the Scientific Evaluation Committee (SEC), and 52 pre-proposals were selected and fully submission. Additionally, the 217 were also evaluated by two external experts and reviewed by project coordinators. The 217 were then submitted once again to a second SEC meeting and 22 consortia were selected for funding, for a budget of about 30,5 Mio €, of which 6 Mio € from the European Commission. The first EJP RD joint transnational call, joined by 32 countries, funded multilateral research projects on diagnosis, disease progression and mechanisms of rare diseases to help scientists to build collaboration, common interdisciplinary research, and sharing of expertise, for patients’ benefit.

EJP opens call for candidates for research mobility fellowship and research training workshop

On 3rd February, the European Joint Programme Rare Diseases (EJP RD), opened a call for a research mobility fellowships for PhD students and physician members of ERNs to support their scientific visits abroad to other host institutions in their European Reference Networks (ERN). The research mobility fellowships which will last between 2 weeks up to 3 months. The call will close on 16 March 2020.

EJP RD also opened a call for a research training workshop. Applicants must be affiliated to an EJP RD beneficiary institution, or they have to be affilitated to an ERN full member, or they have, at the time of application, to be an ERN-affilifated partner institution. The candidates with most suitable proposals will be identified for the organisation of a two day research training workshop which will focus on ERN needs. The selected research training workshops will train ERNs researchers and clinicians in ERN relevant innovative training topics, for cross-ERN added value. The research training workshop call will end on 2 March 2020.

ORPHA codes and the work of a German university to improve patient quality life

The University Medical Center Hamburg-Eppendorf used the ORPHA codes and the mandatory ICD coding to optimise patient documentation, and consecutive treatment. Using the ORPHA codes, the University developed an IT tool for electronic patient with rare diseases and accessible within the whole hospital. The IT tool is not only giving a detailed classification of the rare disease, but will also allow in the future research questions, controlling and strategic decisions for health care provider. In 2019, the German University was funded by health insurance companies for its work to improve the life of people living with rare diseases.

Rare disease registry data of the Italian Fruili Venezia Giuli region

An article published by the Value in Health illustrates the registration of rare disease data of the population of the Italian region Friuli Venezia Giulia, which is providing useful information for health planning. The rare disease data registry can be integrated with many health-related administrative databases, and can allow a variety of epidemiological and cost analyses. The article shows how the mentioned registry can be used to follow the detailed real-world care experience of patients with each specific rare disease, to assess the costs related to each step in their care path, identify inefficiencies, optimise care, and reduce waste of resources. The rare disease registry data were linked with information on mortality, hospital discharges, ambulatory care, and drug prescriptions contained in administrative databases.

Implementation of that registry started in 2010, and 4250 participants were registered up to 2017. A total of 2696 patients were living in the region as of January 2017. The overall raw prevalence of rare diseases was 22 per 10,000 inhabitants, with higher prevalence in the pediatric population. The most common disease groups were congenital malformations, chromosomal and genetic syndromes, and circulatory and nervous diseases.

The first case of homozygous familial hypercholesterolaemia in childhood reported in Southeast Europe

An article published in the Atherosclerosis Supplements reports a first case of a rare disease, homozygous familial hypercholesterolaemia (HoFH), in a young patient aged 11, in the Southern of Europe. HoFH is characterised by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent coronary heart disease. The European healthcare system is still not well prepared to treat HoFI optimally. Access to healthcare care and treatment by HoFI patients still differs from country to country in Europe. An effective treatment for HoFH, Mipomersen, was available in the USA up to November 2018, but is now no longer available even in the US. Mipomersen has never been available in Europe. Within Europe, a treatment, Plasma Exchange (PEX) exists in Serbia and Kosovo, however, there is a lack of financial and mutual agreement between the healthcare systems of the two European countries, with consequences as concerns the access to treatment and reimbursement for therapies for patients.

Health Economics

Orphan medicine expenditure in Europe

Orphan medicinal product (OMP) prices are still considered a challenge to the sustainability of healthcare expenditure, following for example the increasing number of OMPs receiving marketing authorisation (MA) annually. A study published in the Orphanet Journal of Rare Diseases was conducted to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure. Analysis were carried out concerning the total pharmaceutical and OMP expenditure in eight European Union (EU) countries, the first five countries of the European union, Austria, Belgium, and Ireland, (using values and volumes), in the branded, non-branded, and overall pharmaceutical market. The increase, than excepted, in spending on orphan drugs, has been highly offset by the reduced spending in the non-branded orphan drug market, and the increased use of cheaper generic and biosimilar drugs.

Orphan Drugs

Committee for Orphan Medicinal Products meeting report on the review of applications for orphan designation December 2019

The COMP adopted 11 positive opinions recommending the following indications for designation as orphan medicinal products to the Europe an Commission:

• Fabry disease
• Sickle cell disease
• Pancreatic cancer
• Cystinuria
• Huntington's disease
• Mucopolysaccharidosis type IVA (Morquio A syndrome)
• Adrenoleukodystrophy
• Non-traumatic subarachnoid haemorrhage
• Systemic sclerosis (Romilkimab)
• Alström syndrome
• Systemic sclerosis (Ziritaxestat)

Consult the meeting report

Meeting highlights from the Committee for Medicinal Products for Human Use 09-12 December 2019

EMA’s human medicines committee (CHMP) recommended three medicines at its December 2019 meeting for:

Beovu (brolucizumab) for the treatment of neovascular (‘wet’) age-related macular degeneration, a disease that affects the central part of the retina at the back of the eye and causes loss of ‘straight-ahead’ vision
Recarbrio (imipenem / cilastatin / relebactam), for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options
Amsparity (adalimumab) received a positive opinion for the treatment of certain inflammatory and autoimmune disorders

EMA's human medicines committee (CHMP) also recommended the following two generic medicines:

Azacitidine Accord (azacitidine), for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia, diseases in which the body produces large numbers of abnormal blood cells
Dexmedetomidine Accord (dexmedetomidine), for the induction of light to moderate sedation of adults in an intensive care unit.

Consult the meeting report

Clinical Trials Study Design

Experts have identified as top research priority the trial design for Focal Cerebral Arteriopathy rare disease

Pediatric stroke investigators identified as their top research priority a clinical trial of corticosteroids for focal cerebral arteriopathy (FCA). FCA is both rare and an acute condition making it infeasible to enroll the large sample sizes needed for standard, confirmatory clinical trials. The experts presented a pragmatic approach to clinical trial design that may inform the approach to other rare disorders. The investigators surveyed pediatric stroke experts to determine the level of evidence that would impact their clinical management of FCA. Incorporating survey results, a randomised, group sequential Bayesian adaptive design, was proposed based on a quantitative radiologic outcome measure (change from baseline in change in the FCA Severity Score). Using accumulating information, the design determines whether intervention is better than control with high probability. On a total of 21 respondents, in 30% of them, there was probability of corticosteroid efficacy making it possible for experts to treat them.

A new human-on-a-chip approach to better tackle rare diseases

An article published by the Drug Discovery Today highlights the challenges of drug development for rare diseases and orphan drugs, which are, to name a few, the high cost of research and the low target population. The article reports on the approach of a human-on-a-chip (HoaC) technology, whose main characteristic are the models human tissues in interconnected in vitro microfluidic devices, and that has the potential to lower the cost of preclinical studies and increase the rate of drug approval by introducing human phenotypic models early in the drug discovery process. Among the HoaC approach results, there are the drug development and disease modeling for rare diseases remains a challenge, and the advances in in vitro modeling has led to development of human-on-a-chip technology.

Ethic, Legal and Social

Ethical, legal, and social issues in rare diseases analysis by an IRDiRC working group

A Working Group of the International Rare Diseases Research Consortium (IRDiRC) carried out a survey on the Ethical, Legal, and Social (ELSI) funding initiatives for rare diseases to list funding mechanisms and potential gaps in the funding process. The other targeted issue is the role of funding partners, such as clinicians, specialists in social science and patient advocacy groups.

Quality of life

Child behaviors to predict posttraumatic stress disorder for parents of children with Autism Spectrum Disorder and Rare Diseases

A study published in the Research in Autism Spectrum Disorder Journal investigated the validity of conceptualising elevated stress in parents of children who exhibit challenging behavior within the framework of post-traumatic stress disorder (PTSD). The mentioned study amongst hypothesis were that parents of children with autism spectrum disorder (ASD), and parents of children with a rare disease, would endorse greater PTSD symptomatology than parents of typically developing (TD) children, and that challenging child behaviours would positively predict PTSD symptomatology. PTSD symptomatology was reported on the side of parents of children with ASD and parents of children with a rare disease than parents of TD children, and challenging child behaviours were predicted PTSD symptomatology in both groups. Challenging behaviours exhibited by children with an ASD or a rare disease have been shown to be associated with elevated parenting stress.

Bioinformatics and biotechnology

Rare disease ciliopathies: phenotyping and subjacent similarities for fast and precise diagnoses

An article of the Journal of Biomedical Informatics pointed out the fact that rare diseases are hardly and precisely diagnosed, and in most cases, with the lack of approved treatment observed. To treat some complex rare diseases, a precision medicine approach is required to stratify patients into homogeneous subgroups in regards of clinical, biological or molecular features. It is recommended to exploit deep phenotyping of patients and a comparison for precise diagnoses, and to develop therapeutic solutions. Experts developed a new pipeline using deep phenotyping to define patient similarity and applied it to ciliopathies, a group of rare and severe diseases caused by ciliary dysfunction. In this situation, there is a case to report, the work of the French national reference center for rare and undiagnosed diseases, a research institute focusing on genetic diseases, which is based at the Necker-Enfants Malades Hospital (Necker Children's Hospital), hosting the Imagine Institute. The clinical data warehouse of the Necker-Enfants Malades Hospital contains on one hand EHR data, and on the other hand, clinical research data. The similarity metrics were computed on both data sources, and were evaluated with two tasks: diagnoses with EHRs and subtyping with ciliopathy specific research data. Researchers obtained a precision of 0.767 in the top 30 most similar patients with diagnosed ciliopathies. Subtyping ciliopathy patients with phenotypic similarity showed concordances with expert knowledge.

Summary of the edition of 07 February 2020

Editorial
Political news
Scientific news
And also...